The zinc-finger hemolymphopoietic-restricted transcription factor, Ikaros, is mutated in some human leukemias. Moreover, genetic deletions of the Ikaros DNA-binding domain were associated with an aggressive T lymphocyte leukemia in mice. Thus, the transcriptional regulation of growth-modulating genes by Ikaros may be an important underlying cause for the development of certain leukemias. Recently, we have collected novel data suggesting that Ikaros transcriptionally regulates the expression of VIP-PACAP receptor 1 (VPAC-1), which has been demonstrated to transmit anti-proliferative signals. Therefore, we propose to investigate the transcriptional regulation of VPAC-1 by Ikaros in T lymphocytes.